Literature Review III Sunday, April 23th 2012

Asysyukriati R. Prawiro

PULMONOLOGY RESIDENT FACULTY MEDICINE UNIVERSITY OF INDONESIA

Mycobacterium other than tuberculosis (MOTT) Non tuberculous mycobacterium (NTM) Atypical mycobacterium (AM) Opportunistic mycobacterium Unclassified mycobacterium Annonymous mycobacterium Environmental mycobacterium

All mycobacterial species other than Mycobacterium tuberculosis complex and M. leprae
Jurnal Tuberkulosis Indonesia. 2004;1:1-52. Am J Respir Crit Care Med. 2007;175:367-416. Arch Pathol Lab Med. 2008;132:1333-40.

MOTT have been known since the time of Robert Koch but historically overshadowed by tuberculosis and dismissed as contaminant With advances in molecular microbiology and knowledge as true pathogens and important causes of human infection Difficult to diagnose and to treat

Am J Respir Crit Care Med. 2007;175:367-416. Arch Pathol Lab Med. 2008;132:1333-40

Family: Mycobateriaceae Ordo : Actynomycetales Ubiquitous in the environment Can cause both asymptomatic infection and symptomatic disease in humans

4 clinical syndromes Lung disease Lymphadenitis Skin/soft tissue/skeletal disease Disseminated disease

Jurnal Tuberkulosis Indonesia. 2004;1:1-52 Am J Respir Crit Care Med. 2007;175:367-416. Indian J Med Res. 2004;120:290-304.

Widely distributed in the environment with high isolation rates worldwide soil, natural water, tap water, water used in showers, surgical solutions, food, birds Human disease is suspected to be acquired from environmental exposures No evidence of animal-to-human or human-tohuman transmissions

Am J Respir Crit Care Med. 2007;175:367-416 Proc Am Thorac Soc. 2006;3:285-92 Am J Respir Crit Care Med. 2011;183:788-824.

Incidence

Incidence rates vary from 1.0 to 1.8 cases per 100,000 persons Have been seen in most industrialized countries Cases ~ HIV

There is not substantially more or better information about MOTT disease prevalence than that published in the 1997 ATS statement Prevalence on MOTT
Am J Respir Crit Care Med. 2007;175:367-416 Proc Am Thorac Soc. 2006;3:285-92 Am J Respir Crit Care Med. 2011;183:788-824.

Another factors

Predisposing factors
Immunocompromized Underlying pulmonary pathology COPD History of Tb ILD / IPF Silicosis Asbestosis Bronchiectasis Cystic fibrosis Cancer

Smoking (>30 pack/year) Alcohol Cardiovascular disease Chronic liver disease Pasca gastrectomi

The most common inf. (pulmonary) MAC/MAI M. kansasii M. abscessus M. xenopi M. malmoense
Jurnal Tuberkulosis Indonesia. 2004;1:1-52 Am J Respir Crit Care Med. 2007;175:367-416 Respirology. 2009;14:12-26

Medicinus. 2008;60-2.

Medicinus. 2008;60-2

ATSIdentified more than 125 MOTT species Daley CL and Griffith DE identified more than 140 MOTT species, at least 40 of which are associated with lung infection slowly growing mycobacteria (SGM) and rapidly growing mycobacteria (RGM) Runyon system 4 categories (description, growth and pigment production)

Int J Tuberc Lung Dis. 2010;14:66571.

Int J Tuberc Lung Dis. 2010;14:66571.

Am J Respir Crit Care Med. 1997;156:1-25

Am J Respir Crit Care Med. 1997;156:1-25

Am J Respir Crit Care Med. 1997;156:1-25

Arch Pathol Lab Med. 2008;132:1333-40

Nontuberculous mycobacteria. [cited 2010 June 24th]. Available from:URL:http://knoll.google.com/k/nontuberculous-mycobacteria#.

http://knoll.google.com/k/nontuberculous-mycobacteria#.

Port de entry

Port de entry lymph reg

Abrasions in the skin (esp. M.

marinum) Surgical incisions (esp. central catheters) Oropharyngeal mucosa (cervical ) Gastrointestinal Respiratory tract

Lung infect. ~ MTb

Host defense, mucociliary clearence and tracheobronchial secretion Predisposing factors Granulomatous lession = MTb

AAP Grand Rounds .2003;51:1-6

Jurnal Tuberkulosis Indonesia. 2004;1:1-52 Am J Respir Crit Care Med. 2007;175:367-416.m

Still not completely understood

Pathogenesis 3 important observations (over the past two decades)

1. HIV patientsdisseminated NTM infections typically occurred only after the CD4 T-lymphocyte number < 50/ul 2. HIV-uninfected patient genetic syndromes of disseminated NTM infection associated with specific mutations in IFN & IL-12 synthesis and response pathways
Am J Respir Crit Care Med. 2007;175:367-416.

(IFN- receptor 1 [IFNR1], IFNR2, IL-12 receptor 1 subunit [IL12R1], IL12p40, the signal transducer and activator of transcription1 [STAT1], and the nuclear factor- essential modulator [NEMO]) 3. Association bronchiectasis, body habitus, predominantly in postmenopausal women (e.g., pectus excavatum, scoliosis, mitral valve prolapse)
Am J Respir Crit Care Med. 2007;175:367-416.

1. Pulmonary disease

2. Lymphadenitis
4 clinical syndromes

3. Skin/soft tissue/skeletal

4.Disseminated
Jurnal Tuberkulosis Indonesia. 2004;1:1-52 Am J Respir Crit Care Med. 2007;175:367-416 Respirology. 2009;14:12-26

Not specific

Alike tuberculosis or underlying pulmonary pathology Cough sputum Night sweat Lose apptit Fatigue body weight Hemoptysis Could be with lymphadenophati/hepatosplenomegali

Have predisposing factors

Am J Respir Crit Care Med. 2007;175:367-416. Missouri Department of Health and Senior Services- Communicable Disease Investigation Reference Manual

1 (a) Axial and (b) coronal HRCT images taken at presentation show a nodular and tree-in-bud appearance peripherally in both lungs, more marked on the right side with underlying ground glass opacities

Axial HRCT image shows a marked improvement after nine weeks of treatment

Singapore Med J 2008; 49: e47-9

Am J Clin Pathol 2001;115:755-762

The most common 1-5 years old and cervical lymphadenitis ( head and neck) Typically firm, non-tender, and painless, with nonerythematous overlying skin Non-fluctuant: lymph node suppuration and spontaneous drainage may occur after caseation and necrosis development

Arch Pathol Lab Med. 2008;132:1333-40 Journal of Microbiological Methods. 2008;75:111

Fever, weight loss, fatigue, and malaise are usually absent or minimal. Lymph node involvement typically occurs between six to nine months following the initial infection HIV patient subclinical infection after treatment with antiretroviral

Arch Pathol Lab Med. 2008;132:1333-40 Journal of Microbiological Methods. 2008;75:111

Common etiology : MAC another cased by RGM, M. malmoense, M. kansasii M.haemophilum, M. interjectum, M. palustre, M. tusciae, M. heidelbergense, M. elephantis, M. lentiflavum dan M. bohemicum

Arch Pathol Lab Med. 2008;132:1333-40

AAP Grand Rounds. 2003;51:1-6

The spectrum of STSIs is broad and ranges from chronically draining, localized abscesses/nodules to tenosynovitis to frank osteomyelitis.) Typically indolent, and the clinical course variable Predilection direct inoculation such as penetrating trauma or soilage of open wounds and fractures

Arch Pathol Lab Med. 2008;132:1333-40 Am J Respir Crit Care Med. 2007;175:367-416

STSIs..
Iatrogenically cause infections following intravenous and peritoneal catheters, shunts, intramuscular injections, cosmetic surgery procedures, laser in situ keratomileusis procedures, and postsurgical wounds Minor cutaneous infections may resolve spontaneously during the course of 8 to 12 mo. More serious disease, such as osteomyelitis, will likely progress over time

Arch Pathol Lab Med. 2008;132:1333-40 Am J Respir Crit Care Med. 2007;175:367-416

The most common etiology M. fortuitum, M. abscessus or M. chelonae Other species are associated with certain clinical syndromes
Swimming pool granuloma/ fish tank granuloma Mycobacterium marinum Exposure to some type of marine environment (eg, fish, crustaceans, fish tanks) Presents as granulomatous lesions
Arch Pathol Lab Med. 2008;132:1333-40

 usually

on portions of the extremities prone to abrasions begin as papules that then ulcerate and scar often localized, but some patients can develop a nodular lymphangiitis similar to sporotrichosis
Arch Pathol Lab Med. 2008;132:1333-40

Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths

Burulli ulcer Mycobacterium ulcerans Starts as a pruritic nodule that eventually degenerates into a large Irregular Undermined ulcer Chronic Necrotic skin lesions of the extremities In the tropics and Australia
Arch Pathol Lab Med. 2008;132:1333-40

Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths

CD4 < 50 sel/L Etiology : 95 % MAC The most common symptoms fevers, H night sweats, and weight I loss-- Diarrhea and V abdominal pain, hepatoslenomegali , Mycobacterial spindle cell pseudotumors syndrome

Immunosupresion (transpl, cancer, steroid) Infliximab & etanercept Etiology: MAC, M. kansasii, M. chelonae, M. abscessus & M. haemophilum. Symptoms: fevers Some spesies subcutaneous nodul or abses

N o n H I V

Arch Pathol Lab Med. 2008;132:1333-40 Am J Respir Crit Care Med. 2007;175:367-416.m

Disseminated atypical mycobacterial tuberculosis with generalized cutaneous lesions in a boy with acute lymphoblastic leukemia in remission
AAP Grand Rounds. 2003;51:1-6

Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths

Journal of Infection. 2007;55:484-7

MOTToportunistic in the environment MOTT : All mycobacterial species other than M. tuberculosis complex and M. leprae 3. MOTTdiseasepredisposing factors 4. Port de entry infection Abrasions in the skin, surgical incisions, oropharyngeal mucosa, gastrointestinal, respiratory tract and no evidence of animal-to-human or human-tohuman transmissions.
1. 2.

5.

6.

Clinical manifestation 4 clinical syndromes (pulmonary disease, lymphadenitis, skin/soft tissue/skeletal disease, disseminated disease) The most commont manifestation is pulmonary disease